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Variant: NM_000277.3(PAH):c.1156T>G (p.Tyr386Asp)

CA229361

102537 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 428af0db-e5b5-4ac8-8ef3-d61055a45a3a

HGVS expressions

NM_000277.3:c.1156T>G
NM_000277.3(PAH):c.1156T>G (p.Tyr386Asp)
NC_000012.12:g.102843689A>C
CM000674.2:g.102843689A>C
NC_000012.11:g.103237467A>C
CM000674.1:g.103237467A>C
NC_000012.10:g.101761597A>C
NG_008690.1:g.78914T>G
NG_008690.2:g.119722T>G
ENST00000553106.6:c.1156T>G
ENST00000307000.7:c.1141T>G
ENST00000549247.6:n.915T>G
ENST00000551114.2:n.818T>G
ENST00000553106.5:c.1156T>G
ENST00000635477.1:n.260T>G
ENST00000635528.1:n.671T>G
NM_000277.1:c.1156T>G
NM_000277.2:c.1156T>G
NM_001354304.1:c.1156T>G
NM_001354304.2:c.1156T>G

Likely Pathogenic

Met criteria codes 5
PP4 PP3 PM5 PM2 PM3_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The c.1156T>G (p.Tyr386Asp) variant in PAH has been reported in 1 female, Italian patient - type of PKU not specified, serum Phe = 822umol/L; BH4 responsiveness was not specified (PMID: 23430918; PP4). This variant has been detected with R158Q - reported as pathogenic in ClinVar (VarID:587), 14 submitters, phase unknown - 0.5 points (PMID: 23430918; PM3_Supporting). Another missense change at the same amino is pathogenic (p.Tyr386Cys). This variant is absent from population databases (PM2) and is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.977 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3, PP4, PM3_Supporting.
Met criteria codes
PP4
PMID: 23430918 - Y386D reported in 1 female, Italian patient - type of PKU not specified, serum Phe = 822umol/L; BH4 responsiveness was not specified
PP3
Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.977.
PM5
At the same codon as c.1157A>G (p.Tyr386Cys) pathogenic by ClinGen PAH VCEP
PM2
Variant absent from population databases.
PM3_Supporting
PMID: 23430918 - Y386D detected with R158Q - reported as pathogenic in ClinVar (VarID:587), 14 submitters, phase unknown - 0.5 points
Approved on: 2022-06-24
Published on: 2022-06-28
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